The long range goal of this program is to develop and market mouse antiidiotypic (anti-id) monoclonal antibodies (MoAb) which bear the internal image of human high molecular weight-melanoma associated antigen (HMW-MAA) for active specific immunotherapy in patients with melanoma. This proposal stems from investigations in BALB/c mice which have shown that conjugation to KLH and administration with an adjuvant markedly enhances the ability of the mouse anti-id MoAb MK2-23 to induce humoral and cellular immunity towards the HMW-MAA. The specific goal of this proposal is to determine the effect of conjugation with KLH and/or administration with BCG of mouse anti-id MoAb MK2-23 (which bears the internal image of HMW-MAA) on the induction of humoral anti HMW-MAA immunity in patients with melanoma and to correlate the development of anti HMW-MAA immunity with the clinical course of the disease. The data obtained to date in mouse studies and limited clinical trials indicate that immunization of individuals with anti-id MoAb bearing the internal image of HMW-MAA can induce specific immune responses to this antigen. Moreover, the clinical trials have demonstrated an association between anti HMW-MAA immunity and prolonged patient survival. These investigations are designed to optimize the immunization protocols with anti-id MoAb and provide further evidence for the feasibility of this approach in the active specific immunotherapy of patients with melanoma.